项目名称: HRZ三联抗痨药及TGF-β1siRNA脂质体纳米微粒的构建及体内体外实验研究
项目编号: No.81501903
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 牛宁奎
作者单位: 宁夏医科大学
项目金额: 18万元
中文摘要: 以HRZ为基础的抗痨主药在椎体硬化区及其所包裹的结核病灶内很难长期存留及维持有效的药物浓度,抗痨时间长、毒副作用大、顺应性差、督导困难以及宿主细胞抗结核能力差等都是结核迁延不愈和复发的主要原因。因此,开发新剂型高效抗痨药物,改善其在病椎的生物分布,对提高脊柱结核的治愈率、化疗疗效的提供意义重大。本研究拟利用脂质体形成的自组装特性载HRZ并通过与TGF-β1 siRNA结合,形成稳定的脂质体纳米微粒,分析该纳米微粒理化特性、表征及TGF-β1 siRNA靶向基因沉默作用,并在巨噬细胞及兔脊柱结核模型上进行安全性及体内、体外抗结核疗效评价,以期获得缓释、低毒、靶向、易于督导、不易耐药的新型抗结核纳米微粒,为提高脊柱结核疗效、增加病灶区抗结核药物浓度及脊柱结核的基因治疗提供理论基础。
中文关键词: 脂质体;表皮转化生长因子β1;小干扰RNA;抗结核药
英文摘要: The first line anti-tubercular drugs with HRZ are hard to maintain long-term retention and effective drug concentration in the main area of vertebral sclerosis and tuberculosis in the kitchen wrapped.Addition,anti-tuberculosis for a long time, drug side effects, poor compliance, supervision difficulties and poor anti-TB action of host cells are all the main reasons for the delayed healing and recurrence of tuberculosis. Therefore, it is very useful and significant to develop a new form of highly active anti-tubercular drugs, to improve their biodistribution in vertebral, to improve the cure rate of spinal tuberculosis and effect of chemotherapy. In this study, we use of self-assembly properties of liposome to carry HRZ and co-delivery of TGF-β1 siRNA. After the formation of a stable liposomes,we analyze the physical properties, chemical properties, characterization and effective of TGF-β1 siRNA targeted gene silencing of the nanoparticles. We also do the in vivo and in vitro study of anti-tubercular efficacy by evaluation on macrophages and rabbit model of spinal tuberculosis. The purpose of this study is to obtain sustained-release, low toxicity, targeted well, easy supervision, and no drug resistance nanoparticles. The novel synthetic targeting liposomes represent an efficacy of spinal tuberculosis,increase the concentration of anti-tubercular drugs in spinal tuberculosis lesions, and also provide a theoretical basis for the potential treatment of TB gene therapy.
英文关键词: liposomes;TGF-β1;siRNA;anti-tubercular drugs